Copying DNA


copying dna.jpg
copying dna.jpg
The process by which a cell duplicates its genomic DNA to pass on to its daughter cells is known as DNA replication.  Before cell division can occur, the DNA helix must be separated into its constituent strands.  The two strands have different directionality from the replication center– and because of this, they are duplicated via different mechanisms.  The leading strand is synthesized continuously while the other so-called lagging strand, is synthesized via short DNA fragments that are subsequently joined to produce a continuous DNA strand.  Despite this difference in mechanism, the two strands are copied at the same overall rate.  Until now, just how this feat is accomplished by the cell was not clearly understood.

Research performed at the laboratories of Professor Taekjip Ha in the Department of Physics at the University of Illinois, Urbana-Champaign and Professor Smita S. Patel in the Department of Biochemistry at Robert Wood Johnson Medical School using state-of-the-art single-molecule and ensemble methods recently solved this problem by discovering mechanisms that help coordinate DNA replication (Nature 462: 940-943, 2009).  They show that formation of a loop in the lagging strand allows the enzyme that copies DNA to quickly begin synthesis of short DNA fragments (as shown in the figure).  Furthermore, they reveal that faster synthesis of the lagging strand enables it to keep up with the leading strand.  

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1/16/2014 Jonathan Damery, ECE ILLINOIS

“Ten hours, eleven hours,” graduate student Paul Froeter (BSEE '11) was at his computer, clicking through a video and counting the time that it took a strand of a cortical neuron to grow across the frame. The feathery terminus of the neuron waved about, as if feeling for a path forward. Then it found one, a small tube of silicon nitride, and “it shot halfway through the tube,” Froeter said excitedly. “It takes 11 hours for it to travel 40 microns [outside], and then only 30 minutes for it travel 25 microns through the tube. It’s such a fast rate.” 

Associate Professor Xiuling Li and graduate student Paul Froeter holding multielectrode arrays.
Associate Professor Xiuling Li and graduate student Paul Froeter holding multielectrode arrays.
Froeter is working in the research group of Associate Professor Xiuling Li, and recently, they were named the inaugural recipients of the Andrew T. Yang Research Award, which will allow Froeter to focus on this project, essentially developing stents that could guide the growth of neurons in the cerebral cortex of the brain. Once the technology is developed and implemented, functional losses associated with neural damage might be restored. Those who suffer from Alzheimer’s might be able to create and retain memories. Physicians could stymie damage to myelin, the neuron’s protective coating, which is associated with multiple sclerosis. The list goes on.

For Froeter, an Army veteran, the promise of this technology being used to reconnect severed nerves is particularly motivating. As an undergraduate student in the department, he was called to go overseas with the Army a semester before graduation. “When I came back from theater, I wanted to do something to help the rest of the guys over there,” Froeter said. This research could have direct application in the treatment of war-related traumatic brain injury.

The tubes—or rather microtubes, as they’re called—are created through a self-rolling process. This mechanism is induced by releasing built-in strain and causes the microtube to conform around the neuron. If the microtube was too restrictive, it could cut off blood flow and cause cell degeneration, but “fortunately, [the microtubes] will expand naturally based on whatever is inside of it,” Froeter said. “So it prevents blood clots.” This also provides much higher sensitivity than existing neural-electrical devices, including planar electrode arrays. 

With the correct arrangement of the self-rolling microtubes, Li and Froeter hope to grow a network of neurons in vitro, which could then be implanted into a patient. “That’s totally shooting for the moon,” Froeter said, “It’s going to be quite a bit of work, [but] I think by the time that we’re done with it, we should have a good platform for a lot of people to do breakthrough studies on, not just us.”

For the tests, cortical neurons and silicon nitride pads are placed on a device known as a multielectrode array, a thin, two-inch square of glass, which uses embedded electrodes to monitor the signals transferred between the neurons. With precise monitoring, the team hopes to optimize and expedite growth of a connected network of neutrons. “We hope to form a nice network that communicates all in a circle, and that we can track as they talk to each other,” Froeter said. 

As Froeter's video revealed, the neuron grew slowly outside of the tube, and seemed to be waving from side to side, but once it entered the tube, there was only one direction to go: forward. The length of each microtube and the intermittent gaps between them is therefore quite important in terms of optimization, but the reason for the rapid growth within the tube is yet unknown, although strong hypotheses exist. 

This project is a biomedical application of self-rolling tubes that Li’s team initially created for on-chip spiral inductors. Among the differences between these devices is the number of coils. For the inductors, as many as 55 are required, but for the neural application, they use only one or two. The relatively simple fabrication method also means that many diverse applications could arise. “Strain induced self-rolled-up membrane technology enables a 3D hierarchical architectural platform, without introducing 3D fabrication complexity,” Li said. “It can potentially transform the miniaturization and performance enhancement of many devices, from electronics, photonics, to energy harvesting.” 

As the first biomedical application that Li’s team has pursued, this project was fitting for the Andrew T. Yang Research Award, which was established last year with a $1 million gift from alumnus and Apache Design Solutions co-founder Andrew Yang (MSEE ’86, PhD ’89). Yang wanted to encourage ECE students to take on risky, innovative projects that could lead to early entrepreneurial success. Funding is provided for up to two years. 

“Nobody in the group works on bio stuff at this point,” Froeter said. “It’s great because it gives us so many more routes to take our research. It makes the base of our pyramid a little bit wider.” They’ve partnered with researchers from the School of Molecular and Cellular Biology on campus, and also with biomedical engineers at the University of Wisconsin. 

“Once it’s established,” Froeter said, “it’ll be a growth platform to [culture] any cells.”